PDP1
Katalitska podjedinica 1 piruvat-dehidrogenaze (PDPC 1), znana i kao protein-fosfataza 2C, je enzim koji je kod ljudi kodiran genom PDP1.[5][6] PDPC 1 je enzim koji pruža povratne efrkte piruvat-dehidrogenaznih kinaza nakon piruvat-dehidrogenaze, aktivirajući piruvat dehidrogenazu.
Aminokiselinska sekvenca uredi
Dužina polipeptidnog lanca je 537 aminokiselina, а molekulska težina 61.054 Da.[7].
| 10 | 20 | 30 | 40 | 50 | ||||
|---|---|---|---|---|---|---|---|---|
| MPAPTQLFFP | LIRNCELSRI | YGTACYCHHK | HLCCSSSYIP | QSRLRYTPHP | ||||
| AYATFCRPKE | NWWQYTQGRR | YASTPQKFYL | TPPQVNSILK | ANEYSFKVPE | ||||
| FDGKNVSSIL | GFDSNQLPAN | APIEDRRSAA | TCLQTRGMLL | GVFDGHAGCA | ||||
| CSQAVSERLF | YYIAVSLLPH | ETLLEIENAV | ESGRALLPIL | QWHKHPNDYF | ||||
| SKEASKLYFN | SLRTYWQELI | DLNTGESTDI | DVKEALINAF | KRLDNDISLE | ||||
| AQVGDPNSFL | NYLVLRVAFS | GATACVAHVD | GVDLHVANTG | DSRAMLGVQE | ||||
| EDGSWSAVTL | SNDHNAQNER | ELERLKLEHP | KSEAKSVVKQ | DRLLGLLMPF | ||||
| RAFGDVKFKW | SIDLQKRVIE | SGPDQLNDNE | YTKFIPPNYH | TPPYLTAEPE | ||||
| VTYHRLRPQD | KFLVLATDGL | WETMHRQDVV | RIVGEYLTGM | HHQQPIAVGG | ||||
| YKVTLGQMHG | LLTERRTKMS | SVFEDQNAAT | HLIRHAVGNN | EFGTVDHERL | ||||
| SKMLSLPEEL | ARMYRDDITI | IVVQFNSHVV | GAYQNQE |
Funkcija uredi
Piruvat-dehidrogenaza (E1) jedna je od tri komponente (E1, E2 i E3) velikog kompleksa piruvat-dehidrogenaza. Piruvat-dehidrogenazne kinaze kataliziraju fosforilaciju ostataka serina E1 da inaktiviraju komponentu E1 i inhibiraju kompleks. Fosfataze piruvat-dehidrogenaze kataliziraju defosforilaciju i aktivaciju komponente E1 za poništavanje učinaka piruvat-dehidrogenaznih kinaza.
Piruvat-dehidrogenazna fosfataza je heterodimer koji se sastoji od katalitske i regulatorne podjedinice. Prijavljene su dvije katalitske podjedinice; jedna je pretežno ekaprimirana u skeletnim mišićima, a druga je mnogo obilnija u jetri. Katalitska podjedinica, kodirana ovim genom, prva je i pripada superporodici proteinskih fosfataza 2C (PP2C). Uz kompleks piruvat-dehidrogenaze i piruvat-dehidrogenazne kinaze, ovaj enzim se nalazi u mitohondrijskom matriksu.[5]
Regulacija uredi
Fosfatazu piruvat-dehidrogenaze stimuliraju insulin, PEP i AMP, ali je kompetitivno inhibirana pomoću ATP , Nikotinamid adenin-dinukleotida (NADH-a) i Acetil-CoA.
Klinički značaj uredi
Mutacija u ovom genu uzrokuje nedostatak piruvat-dehidrogenazne fosfataze.[5]
Reference uredi
- ^ a b c GRCh38: Ensembl release 89: ENSG00000164951 - Ensembl, maj 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000049225 - Ensembl, maj 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ a b c "Entrez Gene: pyruvate dehydrogenase phosphatase catalytic subunit 1".
- ^ Lawson JE, Niu XD, Browning KS, Trong HL, Yan J, Reed LJ (Sep 1993). "Molecular cloning and expression of the catalytic subunit of bovine pyruvate dehydrogenase phosphatase and sequence similarity with protein phosphatase 2C". Biochemistry. 32 (35): 8987–93. doi:10.1021/bi00086a002. PMID 8396421.
- ^ "UniProt, Q9P0J1" (jezik: engleski). Pristupljeno 20. 9. 2021.
Dopunska litErarur uredi
- Piccinini M, Mostert M, Alberto G, Ramondetti C, Novi RF, Dalmasso P, Rinaudo MT (Apr 2005). "Down-regulation of pyruvate dehydrogenase phosphatase in obese subjects is a defect that signals insulin resistance". Obesity Research. 13 (4): 678–86. doi:10.1038/oby.2005.76. PMID 15897476.
- Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, Yamamoto J, Sekine M, Tsuritani K, Wakaguri H, Ishii S, Sugiyama T, Saito K, Isono Y, Irie R, Kushida N, Yoneyama T, Otsuka R, Kanda K, Yokoi T, Kondo H, Wagatsuma M, Murakawa K, Ishida S, Ishibashi T, Takahashi-Fujii A, Tanase T, Nagai K, Kikuchi H, Nakai K, Isogai T, Sugano S (Jan 2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes". Genome Research. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC 1356129. PMID 16344560.
- Hu RM, Han ZG, Song HD, Peng YD, Huang QH, Ren SX, Gu YJ, Huang CH, Li YB, Jiang CL, Fu G, Zhang QH, Gu BW, Dai M, Mao YF, Gao GF, Rong R, Ye M, Zhou J, Xu SH, Gu J, Shi JX, Jin WR, Zhang CK, Wu TM, Huang GY, Chen Z, Chen MD, Chen JL (Aug 2000). "Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning". Proceedings of the National Academy of Sciences of the United States of America. 97 (17): 9543–8. Bibcode:2000PNAS...97.9543H. doi:10.1073/pnas.160270997. PMC 16901. PMID 10931946.
- Auffray C, Behar G, Bois F, Bouchier C, Da Silva C, Devignes MD, Duprat S, Houlgatte R, Jumeau MN, Lamy B (Feb 1995). "[IMAGE: molecular integration of the analysis of the human genome and its expression]". Comptes Rendus de l'Académie des Sciences, Série III. 318 (2): 263–72. PMID 7757816.
- Lejeune F, Li X, Maquat LE (Sep 2003). "Nonsense-mediated mRNA decay in mammalian cells involves decapping, deadenylating, and exonucleolytic activities". Molecular Cell. 12 (3): 675–87. doi:10.1016/S1097-2765(03)00349-6. PMID 14527413.
- Cameron JM, Maj M, Levandovskiy V, Barnett CP, Blaser S, Mackay N, Raiman J, Feigenbaum A, Schulze A, Robinson BH (Apr 2009). "Pyruvate dehydrogenase phosphatase 1 (PDP1) null mutation produces a lethal infantile phenotype". Human Genetics. 125 (3): 319–26. doi:10.1007/s00439-009-0629-6. PMID 19184109. S2CID 20251714.
- Maj MC, MacKay N, Levandovskiy V, Addis J, Baumgartner ER, Baumgartner MR, Robinson BH, Cameron JM (Jul 2005). "Pyruvate dehydrogenase phosphatase deficiency: identification of the first mutation in two brothers and restoration of activity by protein complementation". The Journal of Clinical Endocrinology and Metabolism. 90 (7): 4101–7. doi:10.1210/jc.2005-0123. PMID 15855260.
- Sugden MC, Holness MJ (maj 2003). "Recent advances in mechanisms regulating glucose oxidation at the level of the pyruvate dehydrogenase complex by PDKs". American Journal of Physiology. Endocrinology and Metabolism. 284 (5): E855-62. doi:10.1152/ajpendo.00526.2002. PMID 12676647.
- Kato J, Kato M (Mar 2010). "Crystallization and preliminary crystallographic studies of the catalytic subunits of human pyruvate dehydrogenase phosphatase isoforms 1 and 2". Acta Crystallographica Section F. 66 (Pt 3): 342–5. doi:10.1107/S1744309110003131. PMC 2833053. PMID 20208177.
- Korotchkina LG, Patel MS (Jun 1995). "Mutagenesis studies of the phosphorylation sites of recombinant human pyruvate dehydrogenase. Site-specific regulation". The Journal of Biological Chemistry. 270 (24): 14297–304. doi:10.1074/jbc.270.24.14297. PMID 7782287.
- Stellingwerff T, Spriet LL, Watt MJ, Kimber NE, Hargreaves M, Hawley JA, Burke LM (Feb 2006). "Decreased PDH activation and glycogenolysis during exercise following fat adaptation with carbohydrate restoration". American Journal of Physiology. Endocrinology and Metabolism. 290 (2): E380-8. doi:10.1152/ajpendo.00268.2005. PMID 16188909.
- Ito M, Kobashi H, Naito E, Saijo T, Takeda E, Huq AH, Kuroda Y (Jul 1992). "Decrease of pyruvate dehydrogenase phosphatase activity in patients with congenital lactic acidemia". Clinica Chimica Acta; International Journal of Clinical Chemistry. 209 (1–2): 1–7. doi:10.1016/0009-8981(92)90327-M. PMID 1327585.
- Adams MD, Kerlavage AR, Fleischmann RD, Fuldner RA, Bult CJ, Lee NH, Kirkness EF, Weinstock KG, Gocayne JD, White O (Sep 1995). "Initial assessment of human gene diversity and expression patterns based upon 83 million nucleotides of cDNA sequence". Nature. 377 (6547 Suppl): 3–174. PMID 7566098.
- Caruso M, Maitan MA, Bifulco G, Miele C, Vigliotta G, Oriente F, Formisano P, Beguinot F (Nov 2001). "Activation and mitochondrial translocation of protein kinase Cdelta are necessary for insulin stimulation of pyruvate dehydrogenase complex activity in muscle and liver cells". The Journal of Biological Chemistry. 276 (48): 45088–97. doi:10.1074/jbc.M105451200. PMID 11577086.
- Bonaldo MF, Lennon G, Soares MB (Sep 1996). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
- Huang B, Gudi R, Wu P, Harris RA, Hamilton J, Popov KM (Jul 1998). "Isoenzymes of pyruvate dehydrogenase phosphatase. DNA-derived amino acid sequences, expression, and regulation". The Journal of Biological Chemistry. 273 (28): 17680–8. doi:10.1074/jbc.273.28.17680. PMID 9651365.
Vanjski linkovi uredi
- Pyruvate Dehydrogenase Phosphatase na US National Library of Medicine Medical Subject Headings (MeSH)
Ovaj članak uključuje tekst iz Nacionalne medicinske biblioteke Sjedinjenih Država, koji je u javnom vlasništvu.